Glycogen Storage Disease Clinical Trials 2023

What are Glycogen Storage Disease Clinical Trials?

Glycogen storage disease (GSD) is a rare hereditary metabolic disorder where the body is unable to synthesize, break down, and use glycogen due to enzyme deficiencies. It usually presents in babies and small children, but later onset can occur in adults. Common symptoms include hypoglycemia, enlarged liver, a swollen belly, stunted growth, and weak muscles.

GSD is classified based on the enzymes missing. There are 15 different types, and the most prevalent are listed below:

• Type I, also known as von Gierke disease, is the most common type of GSD. Here, the liver enzyme glucose-6-phosphatase (G6PC) is missing. Generally, it first appears in 3 to 4-month-old babies.
• Type II, also called Pompe disease, leads to the buildup of glycogen in the body's cells due to the missing enzyme acid alpha-glucosidase (GAA). This can be fatal, with most patients dying within the first year of life.
• Type III, also known as Cori disease or Forbes disease, is caused by the lack of the glycogen de-branching enzyme, which stops glycogen from completely breaking down, thus collecting in tissues and the liver.
• Type IV, also called Andersen disease, leads to the formation of abnormal glycogen, which triggers the immune system. This autoimmune response leads to liver cirrhosis and then liver failure. It is fatal in most cases, with patients dying before age 5.

Why Is Glycogen Storage Disease Being Studied Through Clinical Trials?

Estimates suggest that 1 in every 25,000 babies born in the US has some form of glycogen storage disease (GSD). As researchers know that GSD is caused by a gene mutation, the risk of a child being born with GSD increases with a family history in both parents. Such couples planning on having biological children are encouraged to have genetic screening done to rule out hereditary diseases.

Although enzyme replacement therapy has proven helpful, especially for adults with GSD Type 1, there is no cure for other types, such as Pompe's Disease and Andersen's Disease. More research is necessary for enzyme replacement therapy and gene therapy to improve treatment options and increase survival rates, particularly in children.

What Treatment is Available for Glycogen Storage Disease?

Depending on the GSD type a patient presents with, doctors prescribe therapies to manage the symptoms and improve quality of life.

Treatments for later onset GSD that affects the liver are the most promising and can help adults lead normal lives. Therapies include enzyme replacement, lifestyle, and dietary changes (such as eating uncooked cornstarch regularly).

What are Some Recent Glycogen Storage Disease Clinical Trial Breakthroughs?

2021: A clinical trial sponsored by Ultragenyx Pharmaceutical tested the safety and effectiveness of DTX401 in adults with GSD Type 1a. DTX401 is a gene therapy that delivers a stable version of the missing glucose-6-phosphatase enzyme intravenously. All patients showed improved blood glucose levels while oral glucose replacement (uncooked cornstarch) was tapered.

2023: An ongoing clinical trial studying the effectiveness and tolerance of intravenous mRNA-3745 in people with GSD Type 1. This study aims to investigate if mRNA technology can instruct the body to make the missing liver enzyme.